Ascorbic Acid Infusion Improves Cerebrovascular Reactivity in Middle-Aged and Older Adults

Aging is associated with reductions in cerebrovascular reactivity (CVR) and cerebrovascular conductance (CVC), which may contribute to the development of neurodegenerative disease and stroke. In the peripheral vasculature, increased oxidative stress is linked to vascular dysfunction and is ameliorated following infusion of the antioxidant ascorbic acid (AA). However, oxidative stress’ effect on cerebrovascular function in humans is not entirely understood. PURPOSE: To determine whether oxidative stress reduces CVR and CVC in middle-aged and older adults (MA/O). We hypothesized that AA infusion would increase CVR and CVC in MA/O but not young adults (YA). METHODS: Young (18-29 years) and middle-aged and older (55-79 years) adults were recruited for two identical experimental visits. Each visit consisted of the same measures performed both before and after the infusion of either AA or saline (SAL). Middle cerebral artery blood velocity (MCAv) was recorded using a transcranial Doppler ultrasound probe. CVR was tested using a hypercapnia protocol that was achieved with a computer-based gas blender that increased the subjects’ end-tidal partial pressure of carbon dioxide (PETCO2) 9 mmHg above baseline for a 3-minute period. CVR was defined as the percent change in MCAv during hypercapnia divided by the absolute change in PETCO2. CVC was defined as the percent of CVR normalized for the changes in mean arterial blood pressure. Two-way ANOVAs were used to assess the effects of AA and SAL on CVR and CVC. Fisher’s LSD tests were used to assess main and interaction effects when necessary. RESULTS: 8 YA (25 + 2 years) and 14 MA/O (65 + 6 years) completed the experimental visits. There was a significant main effect of condition (pre/post) on CVR following SAL infusion (p = 0.016), and a significant age x condition interaction effect on CVR following AA infusion (p = 0.016). There were no significant main or interaction effects on CVC following SAL infusion, but there was a significant age x condition interaction effect on CVC following AA infusion (p = 0.012). Post hoc testing indicated that the difference in CVR following SAL infusion was due to an increase in YA (3.0 + 0.5 %/mmHg pre vs. 3.8 + 1.1 %/mmHg post, p = 0.047), whereas the difference in CVR following AA infusion was due to an increase in MA/O (3.3 + 1.7 %/mmHg pre vs. 4.1 + 1.9 %/mmHg post, p = 0.006). The difference in CVC was indicated to be due to both lower baseline CVC in MA/O (2.3 + 0.4 %/mmHg YA pre vs. 1.3 + 1.1 %/mmHg MA/O pre, p = 0.019) and an increase in CVC in MA/O following AA infusion (1.3 + 1.1 %/mmHg pre vs. 2.0 + 0.5 %/mmHg post, p = 0.047). CONCLUSION: Our main finding is that AA infusion restores CVR and CVC in MA/O, but not YA. This finding suggests that age-related increases in oxidative stress may impair cerebrovascular function. Supported by NIH Grant P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.